A general method for synthesizing alpha-hydroxy N-acylindoles in one-pot via an acid-catalyzed condensation of a convertible isonitrile with water and various aldehydes is presented. These intermediates were incorporated into poly(alpha-hydroxy acid) copolymers bearing residues with functionalizable side chains, which could be further modified through Cu(I)-catalyzed azide-alkyne cylcoaddition reactions. This versatile synthetic strategy provides access to side chain functionalized poly(alpha-hydroxy acid) copolymers from readily available aldehydes, making it potentially useful as an approach to synthesize biodegradable polymers with new, tunable properties.